Polymeric Electrospun Scaffolds: Neuregulin Encapsulation and Biocompatibility Studies in a Model of Myocardial Ischemia

Abstract

Cardiovascular disease represents one of the major health challenges in modern times and is the number one cause of death globally. Thus, numerous studies are under way to identify effective cell-and/or growth factor-based therapies for repairing damaged cardiac tissue. In this regard, improving the engraftment or survival of regenerative cells and prolonging growth factor exposure have become fundamental goals in advancing these therapeutic approaches.Biomaterials have emerged as innovative scaffolds for the delivery of both cells and proteins in tissue engineering applications. In the present study, electrospinning was used to generate smooth homogenous polymeric fibers, which consisted of a PLGA/NCO-sP(EO-stat-PO) polymer blend encapsulating the cardioactive growth factor, Neuregulin-1 (Nrg). We evaluated the biocompatibility and degradation of this Nrg-containing biomaterial in a rat model of myocardial ischemia. Histological analysis revealed the presence of an initial acute inflammatory response after implantation, which was followed by a chronic inflammatory phase, characterized by the presence of giant cells. Notably, the scaffold remained in the heart after 3 months. Furthermore, an increase in the M2:M1 macrophage ratio following implantation suggested the induction of constructive tissue remodeling. Taken together, the combination of Nrg-encapsulating scaffolds with cells capable of inducing cardiac regeneration could represent an ambitious and promising therapeutic strategy for repairing diseased or damaged myocardial tissue.

Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering

“…Simón-Yarza et al used a polymer blend containing PLGA and six-armed star-shaped poly(ethylene oxide-stat-propylene oxide) with isocyanate end groups (NCO-sP(EO-stat-PO) with 80% EO content, to encapsulate the cardioactive growth factor Neuregulin-1 (Nrg) [124]. The evaluation of the electrospun scaffold with the encapsulated biomaterial was performed in a rat model of myocardial ischemia, regarding biocompatibility, adherence, and degradation.…”

Modulating Immunological Responses of Electrospun Fibers for Tissue Engineering

“…Bioactive strategies involve the delivery of anti‐inflammatory and/or pro‐wound healing molecules. The delivery of soluble pharmacological anti‐inflammatory agents such as dexamethasone (dex), metronidazole or neuregulin‐1 from electrospun fibers was shown to lead to reduced inflammation and foreign body response. Dex loaded PLLA fibers induced the formation of a much thinner inflammatory capsule compared to PLLA fibers after 2 and 4 weeks post implantation .…”

“… Metronidazole‐loaded PCL nanofibers evoked a less severe inflammatory response than pure PCL nanofibers, as indicated by thinner fibrous capsule formation around the scaffold 7 weeks post implantation . In addition, release of the growth factor, neuregulin‐1 (Nrg) from electrospun poly(lactide‐co‐glycolide) (PLGA)‐based fibers led to an increase in the M2:M1 macrophage following 1 month implantation in vivo, suggesting that the initial immune reaction to the scaffold evolved into a more constructive response over time …”

Nanomaterials for Cardiac Myocyte Tissue Engineering

“…For these reasons, PLGA has been extensively used for biological applications. Simon-Yarza et al used PLGA to create a nanofibrous scaffold to encapsulate recombinant human neuregulin-1 beta isoform (Nrg), a cardiovascular growth factor [29]. This growth factor is known to promote cell recruitment, vasculogensis, and CM replication [30].…”

“…Their scaffold was implanted into a myocardial infarcted rat model and successfully integrated into the cardiac tissue. Simon-Yarza et al [29] also report an increase in M2:M1 macrophage ratio as evidence of constructive remodeling of the infarct zone due to their PLGA scaffold.…”